Effect of iodixanol and ioxilan on QT interval and renal function in patients with systolic heart failure

Background

Contrast media (CM) exposure is associated with a substantial risk of arrhythmias and nephrotoxicity. These adverse effects may be exacerbated in high-risk conditions such as heart failure, although no studies have evaluated newer CM agents in this population. This study evaluated the electrophysiologic and renal effects of two newer CM agents, iodixanol and ioxilan, in heart failure patients undergoing angiography.

Methods

Eighty-seven consecutive systolic heart failure patients who received either iso-osmolar iodixanol (n = 44) or low-osmolar ioxilan (n = 43), stratified for concomitant amiodarone, were evaluated for QT interval and serum creatinine changes in comparison to baseline. QT values were corrected according to three formulae: Bazett's correction, Fridericia formula, and Framingham equation.

Results

Baseline patient characteristics were not significantly different in the iodixanol versus ioxilan groups, except for myocardial infarction and renal disease. No significant change in mean QTc was observed after exposure to either CM agent compared to baseline. These results were unaffected by amiodarone. A significant improvement in serum creatinine from baseline was observed in the iodixanol group compared to the ioxilan group (−0.121 ± 0.35 mg/dL vs. 0.033 ± 0.23 mg/dL, respectively; p = 0.045).

Conclusions

No significant change in QTc interval was observed in patients receiving either iodixanol or ioxilan during angiography. Iodixanol appeared to improve short-term renal function in patients with heart failure and should be further investigated.     

Repolarization changes in patients with heart failure receiving cardiac resynchronization therapy-signs of cardiac memory

Background and Purpose

Cardiac memory is known as T-wave inversions and other repolarization changes after a period of altered ventricular activation, previously mainly studied in structurally normal hearts. We investigated repolarization changes in failing hearts undergoing cardiac resynchronization therapy (CRT).

Methods

Electrocardiogram and vectorcardiogram were recorded before and 1 day and 2 weeks after initiation of CRT in 23 patients with heart failure and left bundle-branch block.

Results

After 1 day of CRT, the T vector during intrinsic conduction (left bundle-branch block) had rotated toward the direction of the paced QRS vector; T-vector size had increased with further increase after 2 weeks (T-vector amplitude, 889 ± 277 vs 651 ± 225 μV; T area, 169 ± 70 vs 102 ± 39 μVs; P < .01) accompanied by prolonged repolarization (T peak-to-end, 174 ± 34 vs 127 ± 16; QT interval corrected for heart rate, 541 ± 59 vs 493 ± 33 milliseconds; P < .01).

Conclusions

Repolarization changes are present in patients with heart failure, although less pronounced compared with after right ventricular pacing in structurally normal hearts.     

Mortality rates and modes of death in heart failure patients with reduced versus preserved systolic function

Background

There are conflicting reports regarding the characteristics and mortality rates of heart failure patients with preserved (HFPSF) vs. reduced systolic left ventricular function (SHF).

Methods

We evaluated the clinical profiles, mortality rates and modes of death in 481 consecutive symptomatic heart failure patients. In 317(66%) patients LVEF was < 40% (SHF), and in 164(34%) LVEF ≥ 40% (HFPSF).

Results

Compared to the HFPSF group, SHF patients were predominantly younger males with ischemic etiology and less cardiovascular comorbidities such as obesity, hypertension, diabetes mellitus and atrial fibrillation. Over a mean follow-up period of 2 years, 148(31%) patients died. Overall mortality was similar between the two groups: 53(32%) HFPSF patients and 95(30%) SHF patients died (p = 0.6), even after adjusting for baseline variables, including age, gender and comorbidities (hazard ratio 1.09; 95% confidence interval 0.74-1.61; p = 0.67). In contrast to the similar mortality rates, the modes of death were different. SHF patients had higher death rates due to pump failure compared to the HFPSF group {32/95(34%) vs. 9/53(17%) patients, p = 0.03}. A trend towards higher rate of non-cardiac death was observed in HFPSF group {33/53(62%) patients vs. 45/95(47%) patients, respectively, p = 0.08}. The prevalence of arrhythmic death was similar in both groups {17/95(18%) vs. 10/53(19%) patients, p = 0.9}.

Conclusions

Although the characteristics of HFPSF and SHF patients are distinctively different, the mortality rates are similar. The mode of death is different among the two groups of patients, as pump failure death is significantly higher in SHF patients, while non-cardiac mortality is more prevalent in HFPSF patients.     

Autonomic nervous system dysfunction in advanced systolic heart failure

Background

An alteration of the autonomic nervous system has been described in heart failure (HF). The aim of this study was to assess, compare and relate the impairment of both arms of the autonomic nervous systems, the sympathetic and parasympathetic (SNS and PNS) in a same group of patients.

Methods

We analyzed 23 patients with advanced HF (NYHA III-IV/IV and IV/IV) and EF < 35% who were on the waiting list for heart transplantation. We assessed the SNS by determining cardiac uptake of ¹²³I metaiodobenzylguanidine, and analyzed the heart mediastinum rate (HMR) and the myocardial washout rate (WR). The PNS was assessed by 24-hour Holter ECG recording and subsequent analyses of heart rate turbulence (HRT) in which turbulence onset (TO) and turbulence slope (TS) were determined.

Results

In the study of the SNS, HMR values were1.32 ± 0.12, and WR 0.36 ± 0.1. Higher creatinine levels were associated with a lower WR (r = −0.604; p = 0.02). In the study of the SNP, TO was higher the lower the LVEF (r = −0.410; p = 0.052), and age was associated with a lower TS (r = −0.4; p = 0.059). In the study of the relationships between the SNS and PNS, HMR was correlated in a nearly significant manner with TO (r = −0.399; p = 0.059) and WR with TS (r = −0.447; p = 0.033).

Conclusions

In stable patients with advanced HF (NYHA III-IV and IV/IV), a significant and parallel impairment occurs in both arms of the autonomic nervous system. This could have prognostic implications and would help to prioritize patients on the waiting list for heart transplantation.     

Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex sensitivity in chronic heart failure patients

Background

One of the beneficial effects of exercise training in chronic heart failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic index in CHF. In our hypothesis-generating study we propose that at least part of this effect is mediated by neural afferent information, and more specifically, by exercise-induced somatosensory nerve traffic.

Objective

To compare the effects of periodic electrical somatosensory stimulation on BRS in patients with CHF with the effects of exercise training and with usual care.

Methods

We compared in stable CHF patients the effect of transcutaneous electrical nerve stimulation (TENS, N = 23, LVEF 30 ± 9%) with the effects of bicycle exercise training (EXTR, N = 20, LVEF 32 ± 7%). To mimic exercise-associated somatosensory ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to both feet. TENS and EXTR sessions were held during two successive days.

Results

BRS, measured prior to the first intervention session and one day after the second intervention session, increased by 28% from 3.07 ± 2.06 to 4.24 ± 2.61 ms/mm Hg in the TENS group, but did not change in the EXTR group (baseline: 3.37 ± 2.53 ms/mm Hg; effect: 3.26 ± 2.54 ms/mm Hg) (P(TENS vs EXTR) = 0.02). Heart rate and systolic blood pressure did not change in either group.

Conclusions

We demonstrated that periodic somatosensory input alone is sufficient and efficient in increasing BRS in CHF patients. This concept constitutes a basis for studies towards more effective exercise training regimens in the diseased/impaired, in whom training aimed at BRS improvement should possibly focus more on the somatosensory aspect.     

Appropriateness and complications of the use of spironolactone in patients treated in a heart failure clinic

Objectives

The widespread use of spironolactone in patients with congestive heart failure (CHF) has resulted in side effects and complications. We analyzed a cohort of patients treated by a dedicated CHF team, in order to examine the tolerability and safety of spironolactone in clinical practice.

Methods

We retrospectively evaluated data on 157 patients who were followed by the Heart Failure clinic of whom 100 patients on maximal treatment (all on β blockers, 99% on ACE inhibitors) received spironolactone. The complications following spironolactone use were defined as: hyperkalemia with serum K 5.2 mEq/l; creatinine 2.0 mg/dl; hyponatremia with serum Na 135 mEq/l, hypotension and side effects such as gynecomastia and abdominal pain.

Results

At 1 year follow-up 6 patients developed hyperkalemia (range 5.3-5.9), 4 of them had K > 5.5 mEq/l. Two patients developed hyponatremia. Six patients stopped spironolactone for: 1-gynecomastia, 2-worsening renal failure and hyperkalemia, 2-hyperkalemia (5.9 mEq/l) and 1 for bradycardia. There was an increase in mean creatinine level at 1 year (1.12 ± 0.35 vs. 1.21 ± 0.38 mg/dl, p = 0.02), however, no significant changes were found in GFR (99.9 ± 33.5 vs. 65.7 ± 27.7 ml min^− 1 1.73 m^− 2, p = ns) and potassium (4.5 ± 0.4 vs. 4.6 ± 0.5 mEq/l, p = ns). We found improvement of GFR by > 10% in 19 patients and worsening by > 10% in 38 patients. No patient was hospitalized or required urgent treatment for spironolactone-related side effects.

Conclusions

In patients with CHF on optimal therapy with ACE inhibitors and β blockers appropriate spironolactone use and close follow-up by a dedicated HF team can minimize the risk for adverse events and complications.     

Event-free survival in adults with heart failure who engage in self-care management

Background

Self-care management in heart failure (HF) involves decision-making to evaluate, and actions to ameliorate symptoms when they occur. This study sought to compare the risks of all-cause mortality, hospitalization, or emergency-room admission among HF patients who practice above-average self-care management, those who practice below-average self-care management, and those who are symptom-free.

Methods

A secondary analysis was conducted of data collected on 195 HF patients. A Cox proportional hazards model was used to examine the association between self-care management and event risk.

Results

The sample consisted of older (mean ± standard deviation = 61.3 ± 11 years), predominantly male (64.6%) adults, with an ejection fraction of 34.7% ± 15.3%; 60.1% fell within New York Heart Association class III or IV HF. During an average follow-up of 364 ± 288 days, 4 deaths, 82 hospitalizations, and 5 emergency-room visits occurred as first events. Controlling for 15 common confounders, those who engaged in above-average self-care management (hazard ratio, .44; 95% confidence interval, .22 to .88; P < .05) and those who were symptom-free (hazard ratio, 0.48; 95% confidence interval, .24 to .97; P < .05) ran a lower risk of an event during follow-up than those engaged in below-average self-care management.

Conclusion

Symptomatic HF patients who practice above-average self-care management have an event-free survival benefit similar to that of symptom-free HF patients.     

N-terminal Pro brain natriuretic peptide is a reliable biomarker of reduced myocardial contractility in patients with lamin A/C gene mutations

Background

Recently, concerns have been raised about a possible lack of sensitivity of biomarkers to detect left ventricular (LV) dysfunction in patients with myopathies. We examined the ability of the N-terminal brain natriuretic peptide (NT-proBNP) to detect LV or right ventricular (RV) dysfunction in patients with lamin A/C (LMNA) gene mutations.

Methods

We prospectively measured plasma NT-proBNP in consecutive patients with documented LMNA mutations and age-sex matched controls. All patients underwent standard echocardiography implemented by pulsed tissue-Doppler echocardiography (TDE).

Results

Twenty-three patients were included (10 males, mean age 39.2 ± 18.9 years);10 had previous atrial arrhythmias, 8 had been implanted with cardioverter defibrillator for primary prevention of sudden death, 5 patients were of NYHA class II and 18 of NHYA class I. Sinus rhythm was recorded in all. NT-proBNP was increased in LMNA patients versus controls (123 ± 229 versus 26 ± 78 pg/ml, p = 0.0004); 7 patients had depressed LV and/or RV contractility. Patients with reduced LV or RV contractility had increased mean NT-proBNP (341 ± 1032 pg/ml versus 80 ± 79 pg/ml in patients with normal myocardial contractility, p = 0.004). Receiver-operating-characteristics analysis shows that NT-proBNP reliably detected depressed contractility (area under the curve 0.889 [0.697-1.000]). Sensitivity and specificity were 88% and 83% respectively, applying manufacturer's recommended cut-off concentration of 125 pg/ml.

Conclusion

NT-proBNP reliably detected the presence of reduced LV/RV contractility in LMNA patients.     

Clinical outcome of patients with heart failure and preserved left ventricular function

Background

Patients with heart failure have a poor prognosis. However, it has been presumed that patients with heart failure and preserved left ventricular function (LVF) may have a more benign prognosis.

Objectives

We evaluated the clinical outcome of patients with heart failure and preserved LVF compared with patients with reduced function and the factors affecting prognosis.

Methods

We prospectively evaluated 289 consecutive patients hospitalized with a definite clinical diagnosis of heart failure based on typical symptoms and signs. They were divided into 2 subsets based on echocardiographic LVF. Patients were followed clinically for a period of 1 year.

Results

Echocardiography showed that more than one third (36%) of the patients had preserved systolic LVF. These patients were more likely to be older and female and have less ischemic heart disease. The survival at 1 year in this group was poor and not significantly different from patients with reduced LVF (75% vs 71%, respectively). The adjusted survival by Cox regression analysis was not significantly different (P = .25). However, patients with preserved LVF had fewer rehospitalizations for heart failure (25% vs 35%, P < .05). Predictors of mortality in the whole group by multivariate analysis were age, diabetes, chronic renal failure, atrial fibrillation, residence in a nursing home, and serum sodium ≤ 135 mEq/L.

Conclusion

The prognosis of patients with clinical heart failure with or without preserved LVF is poor. Better treatment modalities are needed in both subsets.     

Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure

Background

Cardiac resynchronization therapy (CRT) promotes left ventricular (LV) reverse remodelling and affects myocardial collagen turnover in heart failure (HF) patients. Osteopontin (OPN) is a matrix glycoprotein required for the activation of fibroblasts upon TGF-β1 stimulation. In humans, plasma OPN and OPN-expressing lymphocytes correlate with the severity of HF. We sought to evaluate whether plasma OPN and TGF-β1 reflect LV reverse remodelling following CRT.

Methods

Eighteen patients (12 men, mean age 65 ± 11 years) undergoing CRT were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma OPN and TGF-β1. The evaluation was repeated 8.5 ± 4 months after device implantation. Eight healthy age- and sex-matched subjects served as controls.

Results

In HF patients, baseline plasma OPN and TGF-β1 were higher as compared to control subjects (OPN: 99 ± 48 vs 59 ± 22 ng/ml; p < 0.05; TGF-β1: 15.9 ± 8.0 vs 9.3 ± 5.6 ng/ml; p < 0.05). At follow-up, 12 patients responded to CRT and showed LV reverse remodelling, whereas 6 did not. Plasma OPN decreased in CRT responders (108 ± 47 vs 84 ± 37 ng/ml; p = 0.03) and increased in non-responders (79 ± 58 vs 115 ± 63 ng/ml; p < 0.01). TGF-β1 showed a trend towards reduction in responders (17.5 ± 8.7 vs 10.2 ± 8.9 ng/ml; p = 0.08) and was unchanged in non-responders. A significant correlation (r = − 0.56; p = 0.01) was found between relative changes of LVESV and plasma OPN.

Conclusions

CRT-induced LV reverse remodelling is reflected by changes in plasma OPN. Circulating OPN may represent a marker of LV dilation/impairment and an indicator of the response to HF therapies promoting LV reverse remodelling.     

Incidence and mortality of heart failure: A community-based study

Background

Data on the incidence and mortality of heart failure (HF) in community-based populations of developed countries are limited. We estimated the trends of the incidence and, the mortality of HF.

Methods

Prospective population-based study in a white, low-middle class Mediterranean community of 267,231 inhabitants in Spain. Participants were all the patients (= > 14 years), newly diagnosed with HF (4793), according to the Framingham criteria, from January 1, 2000 through December 31, 2007. Main outcome were incidence and mortality following an HF diagnosis.

Results

Incidence of HF increased among both men and women, and among persons with systolic and non-systolic HF. Incidence of HF increased from 296 per 100,000 person-years in 2000 to 390 per 100,000 person-years in 2007 (RR 1.32, CI 95% 1.27-13.7, P < .01). Although, risk-adjusted mortality declined from 2000 to 2007, the prognosis for patients with newly diagnosed HF remains poor. In 2007, risk-adjusted 30-day, 1-year, and 4-years mortality was 12.1%, 28.8%, and 61.4%, respectively. Incidence and mortality of systolic HF were higher than those of non-systolic HF (P < 0.05).

Conclusions

During the last 8 years, in a white, middle class population of the south of Europe, the increased incidence and the decreased mortality of heart failure have resulted in an increased prevalence of heart failure. Incidence and mortality of systolic heart failure were higher than those of non-systolic heart failure.     

Safety and efficiency of chronic ACE inhibition in symptomatic heart failure patients with a systemic right ventricle

Background

ACE inhibition is an established treatment regimen in patients with congestive heart failure due to left ventricular dysfunction which improves morbidity and mortality. However, little is known about the beneficial effects of ACE inhibition in adult patients after Mustard procedure for transposition of the great arteries with heart failure symptoms. Therefore, we investigated the effects of ACE inhibition in these patients on heart failure symptoms, echocardiographic diameters, NT-proBNP and exercise capacity.

Methods

In 14 patients (age 25.2 ± 3.5 years), after Mustard procedure for transposition of the great arteries (age at operation 1.1 ± 1.3 years) with heart failure NYHA II (New York Heart Association class), an ACE inhibition was initiated. At baseline and 13.3 ± 4.0 months after treatment with enalapril (10 mg twice a day), echocardiography, exercise test and NT-proBNP measurements were performed and compared to an age- and sex-matched control group.

Results

Maximum oxygen uptake and echocardiographic parameters did not change significantly in both groups. However, NT-proBNP showed a significant decrease in the treatment group (242 ± 105 vs. 151 ± 93 ng/l, p = 0.004), while in the control group a significant increase (120 ± 89 vs. 173 ± 149 ng/l, p < 0.05) was observed. Furthermore, ACE inhibitor treatment did not result in a deterioration of heart failure symptoms or renal function.

Conclusions

Thus, ACE inhibitor treatment of heart failure symptoms in patients with a systemic right ventricle is safe and reduces NT-proBNP levels significantly as a marker for ventricular overload. Nevertheless, larger scale trials are warranted to show effects on morbidity and mortality in this highly selected patient group.     

Risk Factors for Heart Failure: A Population-Based Case-Control Study

Background

The relative contribution of risk factors to the development of heart failure remains controversial. Further, whether these contributions have changed over time or differ by sex is unclear. Few population-based studies have been performed. We aimed to estimate the population attributable risk (PAR) associated with key risk factors for heart failure in the community.

Methods

Between 1979 and 2002, 962 incident heart failure cases in Olmsted County were age and sex-matched to population-based controls using Rochester Epidemiology Project resources. We determined the frequency of risk factors (coronary heart disease, hypertension, diabetes mellitus, obesity, and smoking), odds ratios, and PAR of each risk factor for heart failure.

Results

The mean number of risk factors for heart failure per case was 1.9 ± 1.1 and increased over time (P <.001). Hypertension was the most common (66%), followed by smoking (51%). The prevalence of hypertension, obesity, and smoking increased over time. The risk of heart failure was particularly high for coronary disease and diabetes with odds ratios (95% confidence intervals) of 3.05 (2.36-3.95) and 2.65 (1.98-3.54), respectively. However, the PAR was highest for coronary disease and hypertension; each accounted for 20% of heart failure cases in the population, although coronary disease accounted for the greatest proportion of cases in men (PAR 23%) and hypertension was of greatest importance in women (PAR 28%).

Conclusion

Preventing coronary disease and hypertension will have the greatest population impact in preventing heart failure. Sex-targeted prevention strategies might confer additional benefit. However, these relationships can change, underscoring the importance of continued surveillance of heart failure.     

Serum visfatin is associated with type 2 diabetes mellitus independent of insulin resistance and obesity

Objective

The aim of this study was to evaluate the association of serum visfatin, adiponectin and leptin with 2 diabetes mellitus (T2DM) in the context of the role of obesity or insulin resistance, which is not well understood.

Methods

A total of 76 newly-diagnosed T2DM patients and 76 healthy control subjects, matched for age, body mass index (BMI) and sex ratio, were enrolled. Anthropometric parameters, glycemic and lipid profile, insulin resistance (measured by homeostasis model assessment of insulin resistance index [HOMA-IR]), leptin, adiponectin, and visfatin were assessed.

Results

On the contrary to adiponectin, serum leptin and visfatin levels were higher in T2DM patients compared with controls (10.07 ± 4.5, 15.87 ± 16.4, and 5.49 ± 2.4 vs. 12.22 ± 4.9 μg/ml, 8.5 ± 7.8 ng/ml and 3.58 ± 2.2 ng/ml, respectively, P < 0.01). Waist circumference and BMI were correlated with leptin and adiponectin but not with visfatin. Leptin, adiponectin and visfatin all were associated with T2DM following adjusting for obesity measures. After controlling for HOMA-IR, visfatin remained as an independent predictor of T2DM (odds ratio = 1.32, P < 0.05). In a multiple regression analysis to determine visfatin only triglycerides and fasting glucose remained in the model (P < 0.05).

Conclusion

Elevation of visfatin in T2DM is independent of obesity and insulin resistance and is mainly determined by fasting glucose and triglycerides.     

Effects of B-Blockers on outcome of patients with Chagas' cardiomyopathy with chronic heart failure

Background

A few studies have shown a beneficial effect of B-Blocker therapy on cardiac function and functional status in patients with chronic heart failure secondary to Chagas' cardiomyopathy.

Methods

The medical charts of patients routinely followed from January, 2000 to January, 2007 were reviewed to collect clinical, standard laboratory tests, 12-lead electrocardiogram, chest X-Ray, and Doppler echochardiogram variables. A Cox proportional hazards model was used to establish independent predictors of all-cause mortality for patients with Chagas' cardiomyopathy with chronic heart failure.

Results

A total of 231 consecutive patients were enrolled in the study. Median follow up was 19 (7, 46) months. Twenty (9%) patients underwent heart transplantation and 120 (52%) died during the investigation. Left ventricular systolic dimension (hazard ratio = 1.04; 95% confidence interval = 1.02 to 1.06; p < 0.005) and need of inotropic support (hazard ratio = 1.80; 95% confidence interval 1.2 to 2.60; p = 0,03), were positively associated, whereas B-Blocker therapy (HR = 0.34; 95% confidence interval 0.23 to 0.51; p < 0.0005) was negatively associated with mortality. Mortality was significantly lower in patients taking in comparison to those not taking B-Blockers. Patients taking a mean daily dose of carvedilol > or = to 9.375 mg had a marked decrease in mortality in comparison to those not on carvedilol therapy.

Conclusion

B-Blockers are effective, not detrimental, and may improve survival in Chagas' disease patients with chronic heart failure. A randomized trial is necessary to confirm these findings.     

Physician attitudes toward end-stage heart failure: a national survey

Background

Despite recent improvements in medical therapies, heart failure remains a prevalent condition that places significant burdens on providers, patients, and families. However, there is a paucity of data published describing physician beliefs about heart failure management, especially in its advanced stages.

Methods

In order to better understand physician decision-making in end-stage heart failure, we used a stratified random sampling of physicians obtained from the Master File of the American Medical Association to survey cardiologists (n = 600), geriatricians (n = 250), and internists/family practitioners (n = 600).

Results

Response rate was 59.6% (highest among geriatricians). The vast majority (>90%) of respondents cited similarities between the clinical trajectory of end-stage heart failure and lung cancer or chronic obstructive pulmonary disease; however, only 15.7% stated that they could predict death at 6 months “most of the time” or “always.” Inpatient volume was a predictor of confidence in predicting mortality (odds ratio = 1.38, 95% confidence interval, 1.36-1.40). Less than one quarter of respondents formally measure quality of life. The experience with deactivation of implantable cardioverter defibrillators was limited: 59.8% of cardiologists, 88.0% of geriatricians, and 95.1% of internal medicine/family practice physicians have had 2 or fewer conversations with patients and families about this option.

Conclusions

Significant gaps in knowledge about and experience with end-stage heart failure exist among a large proportion of physicians. The growing prevalence and highly symptomatic nature of heart failure highlight the need to further evaluate and improve the way in which care is delivered to patients dying from the disease.     

The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy

Background

Cachexia is a common complication of cancer and may be responsible for 22% of all cancer-related deaths. The exact cause of death in cancer cachexia patients is unknown. Recently, atrophy of the heart has been described in cancer cachexia animal models, which resulted in impaired cardiac function and is likely to contribute to mortality. In cancer patients hyperuricaemia independent of tumour lysis syndrome is often associated with a worse prognosis. Xanthine oxidase (XO) metabolizes purines to uric acid and its inhibition has been shown to improve clinical outcome in patients with chronic heart failure.

Methods

The rat Yoshida AH-130 hepatoma cancer cachexia model was used in this study. Rats were treated with 4 or 40 mg/kg/d oxypurinol or placebo starting one day after tumour-inoculation for maximal 15 days. Cardiac function was analyzed by echocardiography on day 11.

Results

Here we show that inhibition of XO by oxypurinol significantly reduces wasting of the heart and preserves cardiac function. LVEF was higher in tumour-bearing rats treated with 4 mg/kg/d (61 ± 4%) or 40 mg/kg/d (64 ± 5%) oxypurinol vs placebo (51 ± 3%, both p < 0.05). Fractional shortening was improved by 4 mg/kg/d (43 ± 3%) oxypurinol vs placebo (30 ± 2, p < 0.05), while 40 mg/kg/d oxypurinol (41 ± 5%) did not reach statistical significance. Cardiac output was increased in the 4 mg/kg/d dose only (71 ± 11 mL/min vs placebo 38 ± 4 mL/min, p < 0.01).

Conclusion

Inhibition of XO with oxypurinol has beneficial effects on cardiac mass and function in a rat model of severe cancer cachexia, suggesting that XO might be a viable drug target in cancer cachexia.     

Elevated NT-proBNP levels should be interpreted in elderly patients presenting with dyspnea

Background

B-type natriuretic peptide (BNP) assay is a useful tool in order to diagnose dyspnea due to congestive heart failure (CHF). On the other hand many other diseases could affect BNP levels. The aim of this study was to investigate a group of elderly patients admitted to an Internal Medicine unit because of dyspnea.

Patients and methods

NT-proBNP was assessed in 132 consecutive patients aged 80 ± 6 years because of dyspnea. History data, anthropometric, clinical and biochemical parameters were collected. Renal function was assessed by the CKD-EPI formula. Diagnosis of pulmonary disease such as infections and chronic obstructive disease was considered and was analyzed as a single parameter. Statistical analysis was carried out dividing patients with high NT-proBNP from those with normal NT-proBNP according to the Januzzi cut-off.

Results

NT-proBNP was higher than the normal reference values in 68.7% of patients and its levels increased in the 5 different stages of chronic kidney disease. Subjects with high NT-proBNP had lower haemoglobin levels (11.6 ± 2.1 vs 12.8 ± 1.9 g/dl, p = 0.003), higher prevalence of atrial fibrillation (54.3 vs 25%, p = 0.001), and lower prevalence of pulmonary diseases (29.7 vs 57.5%, p = 0.005). Logistic regression analysis showed that NT-proBNP levels were independently associated with haemoglobin (OR 1.307 95% CI 1.072-1.593, p = 0.008) and pulmonary diseases (OR 3.069 95% CI 1.385-6.801, p = 0.006).

Conclusions

A disease different from CHF appears to affect NT-proBNP plasma levels. Therefore, determination of its levels does not seem to help clinicians in the definition of dyspnea in elderly people with different comorbidities.     

Comparative study of ambient air particles in patients hospitalized for heart failure and acute coronary syndrome

Introduction and objectives

Currently air pollution is considered as an emerging risk factor for cardiovascular disease. Our objective was to study the concentrations of particulate matter in ambient air and analyze their relationship with cardiovascular risk factors in patients admitted to a cardiology department of a tertiary hospital with the diagnosis of heart failure or acute coronary syndrome (ACS).

Methods

We analyzed 3950 consecutive patients admitted with the diagnosis of heart failure or ACS. We determined the average concentrations of different sizes of particulate matter (<10, <2.5, and <1 μm and ultrafine particles) from 1 day or up to 7 days prior to admission (1 to 7 days lag time).

Results

There were no statistically significant differences in mean concentrations of particulate matter <10, <2.5 and <1 μm in size in both populations. When comparing the concentrations of ultrafine particles of patients admitted due to heart failure and acute coronary syndrome, it was observed that the former had a tendency to have higher values (19 845.35 ± 8 806.49 vs 16 854.97 ± 8005.54 cm⁻³, P <.001). The multivariate analysis showed that ultrafine particles are a risk factor for admission for heart failure, after controlling for other cardiovascular risk factors (odds ratio = 1.4; confidence interval 95%, from 1.15 to 1.66 P = .02).

Conclusions

In our study population, compared with patients with ACS, exposure to ultrafine particles is a precipitating factor for admission for heart failure.Full English text available from: www.revespcardiol.org     

Relation of flow-mediated dilation to global arterial load: Impact of hypertension and additional cardiovascular risk factors

Background

Endothelial dysfunction may be related to increased left ventricular (LV) mass due to an association between endothelial dysfunction with increased arterial load. Therefore, we evaluated whether brachial artery flow-mediated dilation (FMD) is related to global arterial load.

Methods

Pulse pressure/stroke index (PP/SVi, global arterial stiffness, prognostically validated), stroke volume/PP (SV/PP, global arterial compliance), and % of the predicted SV/PP by heart rate, age and body weight (confounder-adjusted global compliance, prognostically validated) were used as LV geometry-related indices of global arterial load.

Results

Compared to normotensive participants (NT, n = 50), those with hypertension (HTN, n = 51) had lower FMD (8.3% ± 5.4 vs. 12.8% ± 6.5), higher PP/SVi (1.24 ± 0.34 vs. 1.04 ± 0.28 mm Hg m²/ml), higher LV mass and higher relative wall thickness (all p < 0.01); in contrast, SV/PP and % of predicted SV/PP did not differ between NT and HTN (all p > 0.1). Impaired FMD was 3-4-fold more prevalent than LV hypertrophy or increased arterial load both in NT and in HTN. Within NT and HTN separately, PP/SVi, SV/PP and % of predicted SV/PP were comparable among tertiles of FMD. Only in NT, lower FMD was associated with higher peak exercise systolic BP (p < 0.05). In multivariable regression models, FMD was not associated with indices of arterial load independently (all p > 0.1).

Conclusions

In young-to-middle-age subjects with cardiovascular risk factors, impaired FMD is more prevalent than traditional preclinical manifestation of cardiovascular disease, and may exist independent to increased arterial load. Thus, endothelial dysfunction assessment may refine cardiovascular risk profile and risk-reduction strategies based on detection of traditional target organ damage.